Daniel F B, Robinson M, Condie L W, York R G
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Cincinnati, Ohio 45268.
Drug Chem Toxicol. 1990;13(2-3):135-54. doi: 10.3109/01480549009018117.
Male and female Sprague-Dawley rats received dibromochloromethane daily by gavage to evaluate its subchronic toxicity. Dose levels were 0, 50, 100, and 200 mg.(kg-day)-1, with 10 animals/sex/group for 90 consecutive days. Corn oil was used as the vehicle. No changes were found in mortality, clinical signs, ophthalmoscopic examinations, or hematology that were considered to be related to treatment. Mean final body weight and body weight gain (weeks 0-13) were significantly decreased in male and female high dose animals relative to the vehicle control. Food consumption was decreased in males in a dose-related fashion, reaching statistical significance at the highest treatment level. Indications of hepatotoxicity in the clinical chemistry included elevated alanine amino-transferase (mid and high dose males) and alkaline phosphatase (high dose males and females). Increased serum creatinine (mid- and high dose males and high dose females) and decreased potassium (high dose males) were considered to be suggestive of nephrotoxicity. Absolute and relative weights of several organs in male and female animals were depressed and were related to the decreased body weights. The decreases in brain and thymic weights, and increases in liver and kidney weight (female only) were considered to be treatment related. Histopathological changes included findings of lipidosis of the liver and slight to moderate degenerative changes within the proximal tubular cells of the kidney. Based on the results of this study, the (LOAEL) lowest observed adverse effect level for DCBM when administered to Sprague-Dawley rats in corn oil gavage was 50 mg.(kg-day)-1.
将雄性和雌性斯普拉格-道利大鼠每日经口灌胃给予二溴氯甲烷，以评估其亚慢性毒性。剂量水平分别为0、50、100和200毫克/（千克·天），每组每种性别各10只动物，连续给药90天。玉米油用作赋形剂。在死亡率、临床体征、眼科检查或血液学方面未发现被认为与治疗相关的变化。与赋形剂对照组相比，雄性和雌性高剂量动物的平均终末体重和体重增加（第0至13周）显著降低。雄性动物的食物消耗量呈剂量相关方式减少，在最高治疗水平时达到统计学显著性。临床化学检查中肝毒性的指标包括丙氨酸氨基转移酶升高（中剂量和高剂量雄性）和碱性磷酸酶升高（高剂量雄性和雌性）。血清肌酐升高（中剂量和高剂量雄性以及高剂量雌性）和钾降低（高剂量雄性）被认为提示肾毒性。雄性和雌性动物的几个器官的绝对重量和相对重量均降低，且与体重减轻有关。脑和胸腺重量的减轻以及肝脏和肾脏重量的增加（仅雌性）被认为与治疗有关。组织病理学变化包括肝脏脂肪变性以及肾脏近端小管细胞内轻微至中度的退行性变化。基于本研究结果，当以玉米油灌胃方式给予斯普拉格-道利大鼠时，二溴氯甲烷的最低观察到有害作用水平（LOAEL）为50毫克/（千克·天）。
